Limits...
Effective antituberculous therapy in a patient with CLIPPERS: New insights into CLIPPERS pathogenesis.

Mélé N, Guiraud V, Labauge P, Oppenheim C, Mas JL, Taieb G - Neurol Neuroimmunol Neuroinflamm (2014)

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (N.M., V.G., J.L.M.) and Department of Neuroradiology (C.O.), Université Paris-Descartes, Sorbonne Paris Cité, INSERM UMR 894, Centre Hospitalier Sainte-Anne, Paris, France; Department of Neurology (P.L.), CHU Montpellier, Hôpital Gui de Chauliac, Montpellier, France; and Department of Neurology (G.T.), CHU Nîmes, Hôpital Caremeau, Nîmes, France.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a brainstem relapsing-remitting inflammatory disease... After 2 months, examination showed only mild left limb ataxia... Brain and spinal MRI (figure 2) showed resolution of enhancing lesions and significant decrease of T2-weighted hyperintensities... In our patient, clinical, MRI, and CSF findings, together with relapse after adequate antituberculous therapy, made the diagnosis of CNS tuberculosis very unlikely... Moreover, M tuberculosis was never found on bacterial analysis... Positive QuantiFERON-TB results only indicate the presence of memory T lymphocytes (directed against tuberculosis antigens), but not necessarily active tuberculosis... Considering that CLIPPERS predominantly concerns white (as opposed to gray) matter on pathologic findings, the mechanism of the facial nerve palsy is probably due to a lesion concerning its fascicle within the brainstem... The repeated clinical and radiologic response to rifampicin/isoniazid/pyrazinamide and the relapse after its withdrawal in our case suggest that antituberculous therapy might be a treatment for CLIPPERS... As CLIPPERS is considered an autoimmune disease, the clinical and radiologic response to antituberculous therapy suggests that CLIPPERS may be a Th17-related autoimmune disease... In inhibiting the Th17 pathway, rifampicin should in theory accelerate the emergence of B-cell lymphoma... Therefore, in contrast to steroid therapy (effective in lymphoma and CLIPPERS), rifampicin might be useful to distinguish these 2 entities... Further studies are needed to confirm the beneficial effect of rifampicin and to better determine the underlying pathophysiology of CLIPPERS.

No MeSH data available.


Related in: MedlinePlus

Spinal MRI in a patient with CLIPPERS treated with antituberculous therapyGadolinium-enhancing lesions (A) and fluid-attenuated inversion recovery (FLAIR) hyperintensities (B) involving the cervical and upper thoracic cord are seen on the initial spinal MRI. After 2 months of antituberculous therapy, enhancing lesions disappeared (C) and FLAIR hyperintensities decreased (D).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4202685&req=5

Figure 2: Spinal MRI in a patient with CLIPPERS treated with antituberculous therapyGadolinium-enhancing lesions (A) and fluid-attenuated inversion recovery (FLAIR) hyperintensities (B) involving the cervical and upper thoracic cord are seen on the initial spinal MRI. After 2 months of antituberculous therapy, enhancing lesions disappeared (C) and FLAIR hyperintensities decreased (D).

Mentions: A 64-year-old man with a history of surgical resection of left thigh fibrosarcoma 5 years ago progressively developed dysarthria, intermittent horizontal diplopia, dizziness, and unsteady gait together with asthenia and anorexia. Ten months after symptom onset (M10), clinical examination showed horizontal bidirectional nystagmus, left facial peripheral nerve palsy, dysarthria, left cerebellar limb ataxia, and ataxic gait. Brain MRI revealed punctate and curvilinear enhancements on gadolinium-injected T1-weighted images involving brainstem, middle cerebellar peduncles, cerebellum, left-sided internal capsule, and corona radiata. Fluid-attenuated inversion recovery (FLAIR) sequences showed hyperintensities in the corresponding areas (figure 1, M10). Spinal MRI disclosed punctate gadolinium-enhancing lesions and patchy T2-weighted hyperintensities in the cervical and upper thoracic cord (figure 2). CSF analysis displayed mild pleocytosis (5/mm3, normal range 0–4/mm3, 95% lymphocytes) and elevated protein level (0.68 g/L, normal range 0.15–0.45 g/L). Oligoclonal bands were absent. CSF cytology, bacterial cultures, and Tropheryma whippelii PCR were negative. QuantiFERON-TB Gold test was positive (AgTB-TN >10 UI/mL, positivity threshold >0.35 UI/mL). Mycobacterium tuberculosis cultures from gastric washings, bronchoalveolar lavage, CSF, and urine were negative. The other extensive laboratory investigations for infectious, inflammatory, and autoimmune (including antiganglioside and onconeural antibodies) diseases were negative. Labial salivary gland biopsy and whole-body fluorodeoxyglucose PET scan showed no evidence of systemic diseases known to involve the CNS. The patient refused brain biopsy. Based on QuantiFERON-TB Gold results, a combination of 3 antituberculosis drugs (rifampicin, isoniazid, and pyrazinamide) (Rifater, Sanofi-Aventis, France) was started without corticosteroids. After 2 months, examination showed only mild left limb ataxia. Brain and spinal MRI (figure 2) showed resolution of enhancing lesions and significant decrease of T2-weighted hyperintensities. Four months later, pyrazinamide was stopped and rifampicin plus isoniazid was continued (Rifinah, Sanofi-Aventis, France). At the end of the 18-month treatment period, the patient was asymptomatic, and brain MRI only showed some hyperintensities on FLAIR images without enhancing lesions (figure 1, M28). Six months later, the patient experienced clinical and radiologic relapse (figure 1, M34). Rifampicin/isoniazid/pyrazinamide was restarted, leading to progressive clinical improvement. Based on clinical and radiologic features of CLIPPERS together with the absence of tuberculosis, antituberculous therapy was stopped. IV bolus of methylprednisolone (1 g daily for 3 days) was started, with marked clinical and radiologic improvement (figure 1, M43).


Effective antituberculous therapy in a patient with CLIPPERS: New insights into CLIPPERS pathogenesis.

Mélé N, Guiraud V, Labauge P, Oppenheim C, Mas JL, Taieb G - Neurol Neuroimmunol Neuroinflamm (2014)

Spinal MRI in a patient with CLIPPERS treated with antituberculous therapyGadolinium-enhancing lesions (A) and fluid-attenuated inversion recovery (FLAIR) hyperintensities (B) involving the cervical and upper thoracic cord are seen on the initial spinal MRI. After 2 months of antituberculous therapy, enhancing lesions disappeared (C) and FLAIR hyperintensities decreased (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4202685&req=5

Figure 2: Spinal MRI in a patient with CLIPPERS treated with antituberculous therapyGadolinium-enhancing lesions (A) and fluid-attenuated inversion recovery (FLAIR) hyperintensities (B) involving the cervical and upper thoracic cord are seen on the initial spinal MRI. After 2 months of antituberculous therapy, enhancing lesions disappeared (C) and FLAIR hyperintensities decreased (D).
Mentions: A 64-year-old man with a history of surgical resection of left thigh fibrosarcoma 5 years ago progressively developed dysarthria, intermittent horizontal diplopia, dizziness, and unsteady gait together with asthenia and anorexia. Ten months after symptom onset (M10), clinical examination showed horizontal bidirectional nystagmus, left facial peripheral nerve palsy, dysarthria, left cerebellar limb ataxia, and ataxic gait. Brain MRI revealed punctate and curvilinear enhancements on gadolinium-injected T1-weighted images involving brainstem, middle cerebellar peduncles, cerebellum, left-sided internal capsule, and corona radiata. Fluid-attenuated inversion recovery (FLAIR) sequences showed hyperintensities in the corresponding areas (figure 1, M10). Spinal MRI disclosed punctate gadolinium-enhancing lesions and patchy T2-weighted hyperintensities in the cervical and upper thoracic cord (figure 2). CSF analysis displayed mild pleocytosis (5/mm3, normal range 0–4/mm3, 95% lymphocytes) and elevated protein level (0.68 g/L, normal range 0.15–0.45 g/L). Oligoclonal bands were absent. CSF cytology, bacterial cultures, and Tropheryma whippelii PCR were negative. QuantiFERON-TB Gold test was positive (AgTB-TN >10 UI/mL, positivity threshold >0.35 UI/mL). Mycobacterium tuberculosis cultures from gastric washings, bronchoalveolar lavage, CSF, and urine were negative. The other extensive laboratory investigations for infectious, inflammatory, and autoimmune (including antiganglioside and onconeural antibodies) diseases were negative. Labial salivary gland biopsy and whole-body fluorodeoxyglucose PET scan showed no evidence of systemic diseases known to involve the CNS. The patient refused brain biopsy. Based on QuantiFERON-TB Gold results, a combination of 3 antituberculosis drugs (rifampicin, isoniazid, and pyrazinamide) (Rifater, Sanofi-Aventis, France) was started without corticosteroids. After 2 months, examination showed only mild left limb ataxia. Brain and spinal MRI (figure 2) showed resolution of enhancing lesions and significant decrease of T2-weighted hyperintensities. Four months later, pyrazinamide was stopped and rifampicin plus isoniazid was continued (Rifinah, Sanofi-Aventis, France). At the end of the 18-month treatment period, the patient was asymptomatic, and brain MRI only showed some hyperintensities on FLAIR images without enhancing lesions (figure 1, M28). Six months later, the patient experienced clinical and radiologic relapse (figure 1, M34). Rifampicin/isoniazid/pyrazinamide was restarted, leading to progressive clinical improvement. Based on clinical and radiologic features of CLIPPERS together with the absence of tuberculosis, antituberculous therapy was stopped. IV bolus of methylprednisolone (1 g daily for 3 days) was started, with marked clinical and radiologic improvement (figure 1, M43).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (N.M., V.G., J.L.M.) and Department of Neuroradiology (C.O.), Université Paris-Descartes, Sorbonne Paris Cité, INSERM UMR 894, Centre Hospitalier Sainte-Anne, Paris, France; Department of Neurology (P.L.), CHU Montpellier, Hôpital Gui de Chauliac, Montpellier, France; and Department of Neurology (G.T.), CHU Nîmes, Hôpital Caremeau, Nîmes, France.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a brainstem relapsing-remitting inflammatory disease... After 2 months, examination showed only mild left limb ataxia... Brain and spinal MRI (figure 2) showed resolution of enhancing lesions and significant decrease of T2-weighted hyperintensities... In our patient, clinical, MRI, and CSF findings, together with relapse after adequate antituberculous therapy, made the diagnosis of CNS tuberculosis very unlikely... Moreover, M tuberculosis was never found on bacterial analysis... Positive QuantiFERON-TB results only indicate the presence of memory T lymphocytes (directed against tuberculosis antigens), but not necessarily active tuberculosis... Considering that CLIPPERS predominantly concerns white (as opposed to gray) matter on pathologic findings, the mechanism of the facial nerve palsy is probably due to a lesion concerning its fascicle within the brainstem... The repeated clinical and radiologic response to rifampicin/isoniazid/pyrazinamide and the relapse after its withdrawal in our case suggest that antituberculous therapy might be a treatment for CLIPPERS... As CLIPPERS is considered an autoimmune disease, the clinical and radiologic response to antituberculous therapy suggests that CLIPPERS may be a Th17-related autoimmune disease... In inhibiting the Th17 pathway, rifampicin should in theory accelerate the emergence of B-cell lymphoma... Therefore, in contrast to steroid therapy (effective in lymphoma and CLIPPERS), rifampicin might be useful to distinguish these 2 entities... Further studies are needed to confirm the beneficial effect of rifampicin and to better determine the underlying pathophysiology of CLIPPERS.

No MeSH data available.


Related in: MedlinePlus